Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

Shultz, Pamela J.; Schorer, Anna E.; Raij, Leopoldo

doi:10.1152/ajprenal.1990.258.1.f162

Cited by 87 publications

(87 citation statements)

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“…In a preliminary study, 42 bradykinin, a known substrate for NEP in vitro, 2 released endothelium-derived relaxing factor and thereby stimulated soluble guanylate cyclase activity and cGMP production in rat mesangial cells. Although the effects of bradykinin on urinary cGMP excretion in vivo have not been demonstrated, previous studies have shown that SQ 29,072 did not potentiate the depressor activity of bolus injections of bradykinin in conscious SHR.…”

Section: Discussionmentioning

confidence: 96%

Potentiation of renal effects of atrial natriuretic factor-(99-126) by SQ 29,072.

Seymour¹,

Fennell²,

Swerdel³

1989

Hypertension

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Depressor and renal activities of atrial natriuretic factor-(99-126) were determined in conscious, unrestrained spontaneously hypertensive rats treated with a neutral endopeptidase inhibitor, SQ 29,amino]heptanoic acid). SQ 29,072 (100 /tmol/kg i.v.) prolonged the transient depressor effects of the peptide for as long as 2 hours. During the first hour after 3, 10, and 30 nmol/kg atrial natriuretic factor, urinary excretion of cyclic 3'5' guanosine monophosphate was significantly increased by 9.2±3.4, 13.0±2.2, and 12.7±4.2 nmol/kg/hr, respectively, in vehicle-treated rats and by 26.9±7.9, 52.1±11.1, and 46.4±12.2 nmol/kg/hr, respectively, in rats given 100 /tmol/kg SQ 29,072. During the first hour after 3 and 10 nmol/kg atrial natriuretic factor-(99-126), the sodium loss was 161±56 and 139±42 /teq/kg/hr in vehicle-treated rats and was significantly greater (694±316 and l,038±135 /teq/kg/hr) in rats given 100 /tmol/kg SQ 29,072. After administration of 3, 10, and 30 /tmol/kg SQ 29,072, the area over the curves of the depressor responses to 3 nmol/kg of the peptide increased from 297±70 to 306±108, 440±143, and 669±186 mm Hgmin, respectively, while the concurrent natriuretic responses rose from 161±56 to 250±88,332±142, 464±164, and 694±316 /teq/kg/hr. In summary, the neutral endopeptidase inhibitor SQ 29,072 increased the magnitudes and especially the durations of the depressor, natriuretic, and cyclic guanosine monophosphate responses to exogenous atria] natriuretic factor-(99-126) in conscious spontaneously hypertensive rats, presumably by inhibition of degradation of atrial natriuretic factor in vivo. In conclusion, neutral endopeptidase inhibition offers an important new technique for enhancement and prolongation of the biological lifetime of atrial natriuretic factor. (Hypertension 1989;14:87-97)

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Section: Discussionmentioning

confidence: 96%

Potentiation of renal effects of atrial natriuretic factor-(99-126) by SQ 29,072.

Seymour¹,

Fennell²,

Swerdel³

1989

Hypertension

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“…In contrast, as the example of nifedipine il lustrates, drug-specific intrarenal effects may antag onize a BP-dependent antiproteinuric action and even counteract the effect of lowering systemic BP. 24,81 On the other hand, the lack of effect of nifedipine on albumin excretion may depend, perhaps in part, on proximal tubular inter actions. 46 Nifedipine caused a marked reduction in fractional lithium reabsorption and a corresponding increase in lithium clearance.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of the Effect of Ace Inhibitors and other Antihypertensive Agents on Proteinuria in Diabetic Patients

Böhlen¹,

Schneider²,

Courten³

et al. 1996

The Kidney and Hypertension in Diabetes Mellitus

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Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression to ward end-stage renal failure. However, some au thors reported disparate renal protective effects of different antihypertensive drugs in diabetic ani mals and humans. In an attempt to resolve the controversy surrounding this possibility, previ ously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca 2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clin ical proteinuria (UProt), treated during >4 weeks with ACE inhibitors, Ca 2+ antagonists, or conven tional therapy (diuretic and/or β-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on av erage -45%) than on conventional therapy (on av erage -23%) or Ca 2+ antagonists other than nifed ipine (on average -35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, Ρ < .05). On the basis of multiple regression anal ysis, ACE inhibitor-induced UProt changes corre lated with BP changes (r = 0.77, Ρ < .00001), aver aged -28% at zero BP change, and varied 1.5% for each percent BP change. On conventional therapy, UProt and BP changes also correlated (r = 0.62, Ρ < .005), but UProt began to decrease only after a BP reduction of >5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors. On Ca 2+ antagonists other than nifedipine, UProt was unchanged at zero BP change, and the regression line for the relationship between changes in UProt (r = 0.55, Ρ < .05) was in an intermediate position between ACE inhibi tors and conventional treatment. Seventy reports also contained data on glomerular filtration rate (GFR). On ACE inhibitors, GFR was on average unchanged, but tended to increase slighty with progressive BP reduction (r = -0.55, Ρ < .0001). On conventional therapy or Ca 2+ .antagonists, vari ations in GFR were unrelated to changes in BP.As ACE inhibitors exert a specific antiproteinuric effect even without a change in systemic BP, they are superior to other agents in treating microalbu minuria or overt proteinuria in initially normoten sive or mildly hypertensive diabetic patients. On the other hand, when systemic BP can be lowered by 20%, as it is desirable in severely hypertensive patients, ACE inhibitors, conventional therapy, and several Ca 2+ antagonists all have a distinct an tiproteinuric action. In contrast, as the example of nifedipine illustrates, drug-specific intrarenal ef fects may antagonize a BP-dependent antiproteinu ric action and even counteract the effect of lower ing systemic pressure. It is of note that ACE inhib itors may, in addition to their antiproteinuric effect, exert a drug-specific beneficial influence on GFR. Am ...

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“…The recent finding that bradykinin increases cyclic GMP and inhibits the contractile response of mesangial cells to Ang II when added to coincubations of mesangial and endothelial cells supports this possibility. 37 The fall in preglomerular resistance seen during the infusion of the kinin antagonist may be secondary to the fall in K { and partial compensation via the rubuloglomerular feedback mechanism.…”

Section: Discussionmentioning

confidence: 99%

Effect of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril.

et al. 1991

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The role of angiotensin II and kinins on the renal cortical and papillary hemodynamic and on the sodium and water excretory responses to converting enzyme inhibition with captopril was examined in euvolemic Munich-Wistar rats. Cortical and papillary blood flows were measured using a laser Doppler flowmeter. Cortical blood flow increased 28% after blockade of angiotensin II receptors with DuP 753 (2 mg/kg i.v., n=6). Captopril (2 mg/kg i.v., n=6) had no effect on cortical blood flow in rats pretreated with the angiotensin II antagonist DuP 753 had no effect on papillary blood flow, nor did it prevent the rise in papillary blood flow produced by captopril (2 mg/kg, n=6). Infusion of a kinin receptor antagonist, r>Arg,[Hyp 3 ,Thi M , D-Phe 7 ]-bradykinin (2.5 /tg/min i.v.), reduced basal papillary blood flow by 15% and blocked the rise in papillary blood flow produced by captopril. Renal blood flow rose by 11% after DuP 753 (2 mg/kg, n=6), and subsequent administration of captopril and the kinin antagonist had no effect on renal blood flow. Urine flow and sodium excretion increased after DuP 753, but captopril produced additional increases in urine flow and sodium excretion of 68% and 46%, respectively. Fractional sodium excretion rose from 0.85±0.15% to 1.56±0.14% after captopril. Infusion of the kinin antagonist returned sodium and water excretion to control levels, but fractional sodium excretion was not significantly altered.' Giomenilar filtration rate was not altered by DuP 753 or captopril; however, it fell from 1.6±0.1 to 1.2±0.1 ml/min/g kidney wt during infusion of the kinin antagonist This fall in giomenilar filtration rate was associated with a 30% fall in the ultrafiltration coefficient These results indicate that captopril alters renal hemodynamics through mechanisms other than blockade of the renin-angiotensin system. In particular, its effects on papillary blood flow and giomenilar dynamics may be due to alterations in the intrarenal levels of kinins. (Hypertension 1991;17:1038-1044) C onverting enzyme inhibitors (CEIs) are antihypertensive agents that promote sodium excretion at lower levels of arterial pressure. However, the mechanisms underlying the natriuretic and antihypertensive actions of CEIs remain uncertain. It generally is thought that these drugs act by blocking the renin-angiotensin system in the kidney and the peripheral vasculature. However, CEIs lower arterial pressure in nephrectomized animals, as well as in rats pretreated with angiotensin (Ang) II antagonists.

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Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

Cited by 87 publications

References 0 publications

Potentiation of renal effects of atrial natriuretic factor-(99-126) by SQ 29,072.

Potentiation of renal effects of atrial natriuretic factor-(99-126) by SQ 29,072.

Comparative Study of the Effect of Ace Inhibitors and other Antihypertensive Agents on Proteinuria in Diabetic Patients

Effect of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril.

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